In this Phase I application, we seek to establish the feasibility of an advanced deterministic approach for solving the radiative transport equation (RTE) for use within a commercially viable small animal optical imaging system. To date, small animal optical imaging using fluorescence and bioluminescence has been confined to non-tomographic planar imaging. However, internal heterogeneties and the non-geometrical propagation of light substantially reduce the effectiveness of these methods for imaging of intra-tissue sources of fluorescence or luminescence. While there have been attempts at predicting light propagation for tomographic small animal imaging using the diffusion approximation, the small volumes and heterogeneities present in mice provide conditions where diffusion theory is not valid. Realizing this, transport based solutions of the RTE have been idenfitied as a promising alternative. However, approaches to date have relied on numerical methods which do not possess the accuracy or efficiency required for effective small animal image reconstruction. In the proposed research, the capabilities and infrastructure of an established commercial radiation transport system provided by Radion Technologies will be leveraged for use in small animal tomographic image reconstruction. Through a combination of third order accurate spatial differencing, robust acceleration methods and the use of arbitrary tetrahedral elements, the proposed approach is well suited for accurately and efficiently modeling both transport and diffusive regimes. This technology will be applied towards modeling fluorescent light generation using frequency-domain photon migration (FDPM) measurements pioneered by the Photon Migration Laboratory at the Texas A&M University. The specific aims of this application are (1) to quantitatively evaluate performance of the proposed approach for forward predictions of FDPM measurements at the excitation and emission (fluorescent) wavelengths; (2) to adapt this approach for image reconstruction, including the extension of an existing adjoint solution method and development of a process control driver; (3) to reconstuct fluorophore absorption cross section mappings from FDPM measurements using (a) weighted back projection and (b) inverse optimization algorithms; and (4) to validate this approach through fluorophore concentration image reconstruction within cross sections of a mouse phantom. Success will be measured on the ability of the proposed approach to accurately reconstruct fluorophore concentrations while having a computational efficiency suitable for ultimate commercial implementation. If successful, Phase 2 will seek to further develop this process towards commercialization and to demonstrate RTE-based imaging of (i) peptide targeted fluorescent contrast agents in xenograft mice with metastatic cancer and (ii) GFR expression in transgenic mice.